BBS Faculty Member - John Blenis

John Blenis

Department of Cell Biology

Harvard Medical School
LHRRB Building, Room 601
240 Longwood Avenue
Boston, MA 02115
Tel: 617-432-4848
Fax: 617-432-1144
Email: jblenis@hms.harvard.edu
Lab Members: 8 postdoctoral fellows, 5 graduate students
Visit my lab page here.



We wish to understand the molecular basis of signal transduction in normal and cancer cells.

Mitogenic/Oncogenic Signaling via Ras and the ERK-MAP kinase/RSK pathway.
Activation of the proto-oncoprotein Ras, results in activation of the Mitogen-Activated Protein Kinases (or ERK-MAPKs) and the ERK-regulated kinases (or RSKs). When improperly regulated, ERK and RSK contribute to a variety of human diseases, including cancer. We are using biochemical, cell biological and RNAi-based approaches to identify new ERK and RSK targets. These data are being used to determine how tERK/RSK contribute to the regulation of immediate-early gene expression, cell migration/invasion, cell proliferation, differentiation, and/or cell survival. We are also examining how temporal regulation and spatial distribution of ERK and RSK contributes to cell context-specific responses and how the Ras signaling system communicates with the G1 cell cycle machinery.

Mitogenic/Oncogenic Signaling via PI3-kinase, mTOR and the S6 protein kinases.
Phosphatidylinositol 3-kinase (PI3K) and mTOR signaling regulate protein translation, cell size/growth, G1 cell cycle progression, and cell survival. To fully understand the molecular basis of mTOR activation and signaling, we have completed high throughput genome-wide RNAi screens and phosphoproteomic screens to define the signaling landscape upstream and downstream of mTOR. This information is being utilized to more fully define how this pathway contributes to diseases such as diabetes, aging and cancer.

Integration of signaling by nutrients, energy sufficiency and growth factors.
Mitogen-regulated signaling pathways converge on distinct nutrient/energy sensing pathways to regulate various critical biological processes. Tumor suppressors mutated in diseases such as tuberous sclerosis (TSC1/2), lymphangioleiomyomatosis (TSC2) or Peutz-Jeghers syndrome (LKB1) regulate signaling to the nutrient/energy sensor mTOR. mTOR is specifically inhibited by the drug rapamycin; an immunosuppressant, inhibitor of restenosis and cancer cell growth. How amino acids, energy sufficiency or cell stress signal to mTOR, and how mitogenic signals and nutrient/energy signals collaborate to regulate mTOR and S6 kinases is under investigation.



Last Update: 8/9/2013



Publications

For a complete listing of publications click here.

 


 

Ma X, Yoon, SO, Richardson CJ, Jülich K, and Blenis J. SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs. Cell 2008; 133: 303–313.

Shin S, Dimitri, CA, Yoon, SO, Dowdle WE and Blenis J. ERK2, but not ERK1, induces epithelial to mesenchymal transformation via DEF motif dependent signaling events. Mol. Cell 2010; 38: 114-127.

Choo AY, Kim SG, Vander Heiden MG, Mahoney SJ, Vu H, Yoon SO, Cantley LC, Blenis J. Glucose addiction of TSC-null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply. Mol Cell. 2010; 38: 487-499.

Mendoza MC, Er EE, Zhang W, Ballif BA, Elliott HL, Danuser G, and Blenis J. ERK-MAPK Drives Lamellipodia Protrusion by Activating the WAVE2 Regulatory Complex. Mol. Cell 2011; 41: 661-671.

Yu Y, Yoon SO, Poulogiannis G, Yang Q, Ma XM, Villén J, Neil Kubica N, Hoffman GR, Cantley LC, Gygi SP and Blenis J. Quantitative Phosphoproteomic Analysis Identifies the Adaptor Protein Grb10 as an mTORC1 Substrate that Negatively Regulates Insulin Signaling. Science 2011; 332: 1322-1326.



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